ABSTRACT Hazardous drinking is a significant public health problem, affecting approximately 20% of U.S. adult primary care patients, contributing to about 65,000 deaths and costing the US health system more than $250 billion annually. Clinical trials have documented the efficacy and cost-effectiveness of Alcohol Screening and Brief Intervention (ASBI), including in the health system studied here, and it is now a widely-endorsed approach to identification and early intervention for hazardous use. However, relatively few studies have examined real-world ASBI implementation and, its long-term sustainability, and their relationship to patient outcomes, utilization and cost. This study will take advantage of an ongoing health system-wide ASBI initiative in a large, heterogeneous health care delivery system, Kaiser Permanente Northern California, which in 2013 incorporated ASBI into its adult primary care workflow and conducts an average of 145,000 screenings and 9,500 brief intervention (BIs) monthly for adult primary care patients. Using a theory-driven conceptual framework, this innovative study will rigorously examine the factors which facilitate or impede successful real- world ASBI implementation and long-term sustainability. Guided by the PRISM (Practical, Robust Implementation and Sustainability Model) framework, this mixed-methods study will use electronic health record (EHR) data from 1/1/2014 to 12/31/2021, along with primary care provider surveys, patient telephone interviews, and qualitative key informant interviews to examine ASBI implementation (1/1/2014 ? 12/31/2015), short-term sustainability (1/1/2016-12/31/2018) and long-term sustainability (1/1/2019 ? 12/31/2021) outcomes (screening and BI rates); patient outcomes (heavy drinking days and typical drinking quantity and frequency, health services utilization and costs); and the fidelity and quality of BIs. We will use the PRISM domains to enhance our understanding of ASBI implementation and long-term sustainability. First, we will employ indirect standardization (observed-to-expected ratios) methodology to benchmark ASBI implementation, short- and long-term sustainability performance over 8 years and examine associating factors. Second, we will conduct multi-level models analyses to determine whether and how ASBI implementation and sustainability are related to patient drinking outcomes and use of health services and costs. Finally, we will measure BI fidelity and quality by asking patients and PCPs about their experiences receiving and delivering BIs, and examine how they are related to patient outcomes. Results will provide concrete, pragmatic guidance on factors which facilitate successful ASBI implementation and long-term sustainability that can be used widely by this and other health systems to improve how we identify and treat the full spectrum of unhealthy alcohol use, and how we implement, sustain and study population-based responses to it.